1. Field of the Invention
The present invention relates to a raw membrane material for medical use and to a method for producing the same.
The invention aims to supply medical raw materials that satisfy conditions which ultimate ideal artificial organs and tissues must possess. The ultimate ideal artificial organs and tissues are artificial materials for treatment, which are applied to the body during surgery and which possess not only mechanical functions, but also the physiological functions of regeneration of homologous materials and defective tissues at lesions. The artificial materials are degraded, absorbed into tissues and replaced simultaneously by normal tissues at lesions, that is, with the synchronous regeneration of defective tissue. These artificial materials are called homologous medical materials for replacement.
2. Discussion of the Prior Art
As reported In scientific papers entitled "The Extracellular Matrix of Human Amniotic Epithelium: Ultrastructure, Composition and Deposition" (J. Cell. Sci., 79: 119-136, 1985) and "Surface Visualization of Tissue Interfaces by Scanning Electron Microscopy: Methods for Exposure of Basal Lamina and Associated Structure In Human Amnion" (Scanning Microscopy Vol. 2, No. 4, Pages 2067-2078, 1988) both written by T. D. Allen and his collaborators at the Department of Ultrastructure, Paterson Institute for Cancer Research, Christie Hospital, Manchester M20 9BK, UK, T. D. Allen et al. studied in detail, using electron microscopic technique, the structure of epithelial, basal, compact and fibroblast layers of human amnion and investigated other substances that comprise the human amnion. The procedures, measures and techniques used by these authors to eliminate cells in their research are summarized below.
Fetal membranes were detached using scissors from placenta of 37-39 weeks gestation that had been removed by cesarean section. The detached fetal membranes were washed 3 times with 100-150 ml phosphate buffered saline. Amnion was separated from chorion using a forceps, after the fetal membrane was heated in phosphate buffered saline for 15-20 minutes in order to relax the adhesion between the two membranes. Washed amnion was treated with 0.2 M ammonium solution approximately 20 times every 5-15 minutes using fresh solution with each treatment. Then, the amnion was treated with 0.2% or 0.1% sodium dodecylsulphate solution for 30 minutes to 2 hours, and then treated with the protease, trypsin. Using the procedure and measures summarized above, a layer of an acellular nature comprising the basement membrane and the compact layer without cells was acquired. The two acellular layers are comprehensively called a basement membrane in microscopic science, and are separately referred to as a basement membrane layer and as a compact layer in physiology. This is the technique used by T. D. Allen et al.
Japanese Patent No. 1,842,777 (Japanese Patent Publication No. 5-50295 i.e., 50295/93), filed claiming convention priority based on U.S. patent application Ser. No. 503,203 of Jun. 10, 1983 and convention priority based on U.S. patent application Ser. No. 582,504 of Feb. 22, 1984, is entitled "Grafts Comprising Extracellular Matrix and Procedure and Method of Manufacturing and Use of Said Grafts". The patent claims: (1) Aseptic grafts comprising biogenic structural bodies, which primarily comprise collagen and elastin and which are in the form of an extracellular matrix in which cell membrane, nucleic acid, lipid and components of cytoplasm have been removed. (2) The graft as claimed in Claim 1 which has a dimension and size such as to conform to tissue structures at sites of the body to which the graft is to be implanted. (3) The aseptic graft as claimed in Claim 1, which has been treated with a detergent immediately after the above-mentioned biogenic structural bodies are removed from body and prior to substantial chemical cross-linking or subsequent changes. The patent contains 28 claims.
In the above-mentioned patent, "graft" and "biogenic structural bodies" are not limited to specific bodies but they may be derived from any living bodies. Long before the above-mentioned patent was applied for, medical products of graft derived from fish, swine or horse, which are similar to those described in the above-mentioned patent, had been on the market throughout the world. Examples are air-bladders of fish, swine pericardium and equine pericardial membranes. These are aseptic grafts comprising biogenic structural bodies which have collagen and elastin as the primary component and are in the form of an extracellular matrix without substances that form cells. In addition, they are products with dimension and sizes that conform to tissue structures at the sites of the body to which the products are applied.
A study published by Kimoto, Sugie, Tsunoda et al. of University of Tokyo in Arch. Surg. 69 (4): 549-563, 1954 and "The use of arterial implants prepared by enzymatic modification of arterial heterografts" by Rosenburg N. et al. in Arch. Surg. 74: 89, 1957, reports the procedure and methods of manufacturing and using grafts that have conditions defined with similar terms as described in claims 1 and 2 of the above-mentioned patent.
U.K. Patent No. 1,565,340 filed Apr. 25, 1978 preceded that of the above-mentioned Japanese Patent No. 1,842,777. Claim 1 of U.K. Patent No. 1,565,340 describes "Fibrous tissue materials of human or animal origin that do not substantially contain antigenic non-fibrous protein and do not substantially contain antigenic polysaccharides or glycoprotein, and that are used as a temporary bandage for skin wounds and soft tissue damages and are suited for heterografts." This invention, in light of medical and biochemical knowledge, is synonymous with "Grafts comprising biogenic structural bodies which primarily comprise collagen and elastin and which are in the form of extracellular matrix in which cell membrane, nucleic acid, lipid and components of cytoplasm have been removed" of the above-mentioned Japanese Patent No. 1,842,777. Furthermore, the detailed description of both patents shows clearly that the objects of both inventions are to provide essentially the same medical materials.
The objects of the reports and patents described above, from a scientific point of view, are to produce similar medical materials. However, different technical measures are employed individually. The technique characteristic in the abovementioned Japanese Patent No. 1,842,777 is interpreted as the procedure and method of using a detergent, which is described in Claims 3 to 26.
The prior art technique described above, which is to acquire objective medical materials, makes use of an inorganic alkaline aqueous solution, a synthetic detergent, trypsin, which is an animal protease, or ficin, which is a plant protease.
However, prior art techniques have been unable to produce a membrane material that is asymmetrical at the front and back sides and that completely satisfies "cell proliferation and cell matrix" which is characteristic of the compact layer membrane of biogenic connective tissue and is a theme in connective tissue science. In other words, prior art techniques have been unable to produce medical materials having physiological function of growing tissue cells necessary for auto-regeneration and repair of damaged tissues and of degradation, absorption and replacement in synchrony with regeneration of tissues.
Development of techniques has been sought eagerly for the manufacturing of membranous materials that have physiological functions of facilitating intake and proliferation of tissue cells, and of degradation, absorption and replacement with regenerated tissues in synchrony with regeneration of damaged tissues. The membranous materials originate from biogenic connective tissue membranes and retain the same form and structure as those of living tissue.